Motor learning forms a foundation for rehabilitation interventions to treat patients with debilitating neurological disorders such as stroke. It is now known that the cerebellum is required for motor adaptations and motor learning. The motor cortex is also involved in motor learning, but its specific role is less clear. Recent studies indicate that the motor cortex may be more involved in the consolidation and/or retention phases of motor learning than in the initial acquisition. It is not known whether individuals with stroke involving the motor cortex have deficits in retention of newly acquired motor adaptations. Broadly, the purpose of this research is to determine the effects of unilateral stroke involving the primary motor output system on retention of a newly learned visuomotor walking adaptation in humans. Motion capture, electromyography and transcranial magnetic stimulation (TMS) will be used to record limb movements and to measure and modulate corticospinal excitability, respectively. In Aim 1, visual feedback during walking will be altered to induce a novel gait pattern in healthy and stroke-affected adults that, in stroke subjects, is designed to improve symmetry of single limb support durations between the legs. Initial adaptation and retention of the new walking pattern will be measured and compared across groups at several time periods. Subject with stroke are expected to show reduced retention but relatively intact adaptation. In Aim 2, low frequency inhibitory repetitive TMS (rTMS) will be applied over the primary motor cortex (M1) of the non- lesioned hemisphere in individuals with stroke prior to walking. Effects of rTMS on the acquisition and retention of the visuomotor walking adaptation will be measured and compared to a group of stroke subjects receiving sham stimulation. Single pulse TMS will be used to measure changes in corticospinal excitability before and after rTMS. We predict that inhibitory rTMS to the non-lesioned M1 will improve retention of the walking adaptation in stroke subjects, and will be associated with disinhibition of the lesioned M1. We also expect to find that the level of benefit from rTMS varies with lesion location. Results from the proposed aims will help determine whether individuals with stroke involving the primary motor output system have deficits in acquisition and/or retention of newly adapted walking patterns and whether this deficit can be temporarily improved using rTMS. This work is particularly important because 1) it will help determine the role of the motor cortex in acquisition and/or retention of motor adaptations, 2) it will support or refute the proposed mechanism of overly strong transcallosal inhibition from the non-lesioned hemisphere as a source of motor impairment in patients with stroke, and 3) it may lead to the development of novel therapies to enhance motor learning and retention in patients with motor disability due to stroke. PUBLIC HEALTH RELEVANCE: Results from these studies will provide novel insights into brain mechanisms of impaired motor learning following stroke. Importantly, findings are expected to help lead to the development of new rehabilitation interventions to enhance motor learning of locomotor patterns in patients with stroke. Thus, this work will have broad impact on public heath, as stroke is a leading cause of long-term disability and leaves many of its victims unable to walk without assistance.